泌尿道致病性大腸桿菌是泌尿道感染, 如膀胱炎、腎盂腎炎、尿路感染引起之菌血症等感染症最主要的致病原。許多傳統的分型方法，包括血清型分析, 以PCR為基礎的基因型分析，脈衝式電泳分型法及多重基因座序列分析法等，都已經廣泛地應用於泌尿道致病性大腸桿菌的分型與鑑定，但是這些方法的鑑別力，遠不如能夠同時偵測大量基因資訊的DNA晶片。因此，我們利用從美國康乃爾大學獲得的寡核苷酸DNA晶片來對泌尿道致病性大腸桿菌進行分子分型。這個DNA晶片含有339個大腸桿菌的基因探針，能夠偵測許多致病性大腸桿菌基因，以及三個標準菌珠（K-12 MG1655, EHEC EDL933及UPEC CFT073）的特有與共有的基因。晶片分析的結果進行差別性層級叢集分析（differential hierarchical clustering）之後，發現造成下泌尿道感染的臨床分離株存有兩個子群（subgroup）。從系統發生學的角度來看，屬於其中一個子群的分離株，是比較接近腸道共生大腸桿菌族群，但屬於另一個子群的分離株，卻比較接近能夠造成上泌尿道感染及尿路型敗血症的分離株。

雖然已經發現許多跟泌尿道感染致病機轉有關的因子，但仍有半數以上的泌尿道致病性大腸桿菌並不具有這些已知的致病基因，或者是僅具有其中之一。於是，我們合理地推測仍有還未被發現的致病因子，參與UPEC入侵泌尿道的機轉；而根據這個推測，我們希望找到新的、跟泌尿道感染致病機轉有關的基因。我們提出一個假設：UPEC的基因如果是跟泌尿道感染有流行病學上的關連性，那麼它很可能就會參與泌尿道感染的致病機轉。根據這個假設，我們找尋分佈率跟泌尿道感染有關連性的基因，為了達到這個目的，我們先利用上述提到的DNA晶片，對一小部分的大腸桿菌進行篩選，希望找出相較於腸道共生大腸桿菌，在泌尿道致病性大腸桿菌有比較普遍分佈的基因。DNA晶片分析的結果找到了6個比較普遍存在於泌尿道致病性大腸桿菌的基因，包括一個由eco58, eco59與eco60組成，受鐵離子調控的操縱元，以及其下游基因eco56，另外，也找到了兩個存在於UPEC CFT073基因組的ORFs。這些基因進一步地以231株泌尿道致病性大腸桿菌，115株腸道內的共生大腸桿菌，以及32株從感染非尿道感染引發之菌血症的病人血液中分離的臨床菌珠，進行大規模的PCR篩選。PCR的結果證實了這些基因是在流行病學上跟泌尿道感染有關聯（P＜0.05），顯示它們很可參與尿道感染的致病機轉，因此值得我們進一步由分子生物學的角度切入研究其可能功能。

Uropathogenic Escherichia coli（UPEC）is responsible for the majority of urinary tract infections（UTIs）, including cystitis, pyelonephritis, and UTI-related bacteremia. Many conventional strain typing methods（such as serotyping, PCR-based genotyping, PFGE and MLST）have been widely employed to characterize and differentiate isolates belonging to the UPEC pathotype, but their discriminatory power is much lower when compared with DNA microarray analysis by which a large quantity of genetic information can be simultaneously acquired. In this study, we utilized the oligonucleotide spotted DNA arrays, which were obtained from Cornell University, to perform molecular subtyping of the UPEC isolates. The arrays contained 339 gene probes, which were able to detect various virulence genes of intestinal and extraintestinal pathogenic E. coli strains, to detect genes respectively specific to the three standard E. coli strains（K-12 MG1655, EHEC EDL933 and UPEC CFT073）, and to detect genes commonly identified in these standard strains. Through differential hierarchical clustering of the microarray results, two subgroups of UPECs causing lower urinary tract infections were identified. One of the subgroups contained isolates phylogenetically closer to the intestinal commensal E. coli population, whereas the other subgroup contained isolates more similar to UPECs causing upper UTIs and urosepsis.

Although various virulence factors involved in uropathogenesis have been identified, as many as half of all E. coli strains causing UTIs were shown to possess none or merely one of the known virulence factors. Accordingly, it is reasonable to speculate that there are still undiscovered virulence factors which are able to facilitate UPECs to invade urinary tract. According to this speculation, we expected to identify potential novel virulence genes associated with uropathogenesis. We proposed a hypothesis that if a gene of uropathogenic E. coli is epidemiologically associated with UTI, it is highly possible that the gene is involved in the pathogenesis of the disease. We planned to identify the E coli genes whose distribution rates are positively associated with UTI. For this purpose, we first employed the array mentioned above to screen a small amount of E. coli isolates for the genes with higher prevalence rates in the UPEC isolates than in the commensal fecal isolates. The microarray array results inferred that an iron-regulated operon consisting of eco58, eco59 and eco60 and its downstream gene eco56 were potentially associated with UTI. Moreover, two putative genes（eco293 and eco294）identified in CFT073 genome might be associated with UTI, too. These genes were further subjected to a large-scale PCR screening of 231 UPEC clinical isolates, 115 commensal strains, and 32 E. coli isolates from blood of the patients with non-UTI bacteremia. The PCR results validated that these genes were urovirulence-associated candidates shown to have epidemiological significance（ P＜0.05）. Thus they are potential virulence genes involving uropathogenesis and worthy of further investigation.

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